A Phase 2 Trial of Ibrutinib and Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin's Lymphoma
概览
- 阶段
- 2 期
- 干预措施
- Ibrutinib
- 疾病 / 适应症
- Classical Hodgkin Lymphoma
- 发起方
- Ohio State University Comprehensive Cancer Center
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Proportion of patients in CR
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
This phase II trial studies how well ibrutinib and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back or has not responded to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Giving ibrutinib and nivolumab may work better in treating patients with classical Hodgkin lymphoma.
详细描述
PRIMARY OBJECTIVES: I. To estimate the complete response (CR) rate with ibrutinib at the standard dose of 560 mg daily in combination with nivolumab 3 mg/kg intravenously (IV) every 3 weeks up to 16 infusions in patients with relapsed or refractory classical Hodgkin lymphoma (cHL). SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) with ibrutinib and nivolumab in combination in patients with relapsed or refractory classical HL. II. To determine safety and toxicity of ibrutinib in combination with nivolumab in patients with relapsed or refractory cHL. III. To determine the progression free survival (PFS) in patients with relapsed or refractory cHL treated with combined ibrutinib and nivolumab. IV. To determine the duration of response in patients with relapsed or refractory cHL treated with ibrutinib in combination with nivolumab. TERTIARY OBJECTIVES: I. To determine the effects of ibrutinib and nivolumab on the distribution of T-, B-, and NK cells in the peripheral blood. II. To determine the effects of ibrutinib and nivolumab on Th1/Th2 cytokines profile and correlate this with treatment response. III. To determine the effects of ibrutinib and nivolumab on Th1/Th2 ration and specific IgG sub-isotypes. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21 and nivolumab IV continuously over 60 minutes on day 1.Treatment with nivolumab repeats every 21 days for up to 16 courses and treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
研究者
Lapo Alinari
Principal Investigator
Ohio State University Comprehensive Cancer Center
入排标准
入选标准
- •Patients with histologically confirmed classical HL that is relapsed or refractory after at least one prior therapy are eligible
- •Patients with lymphocyte predominant Hodgkin's are eligible
- •Prior treatments: patients must have had at least one prior therapy
- •Patients with previous autologous transplant are permitted
- •Patients who are eligible and willing to undergo autologous transplant should not be enrolled on this trial
- •Prior allogeneic transplant is NOT permitted
- •Prior treatment with Bruton's tyrosine kinase (BTK) inhibitors is NOT permitted
- •Prior treatment with nivolumab is permitted
- •Presence of radiographically measurable disease (defined as the presence of a \>= 1.0 cm lesion, as measured in the longest dimension by computed tomography \[CT\] scan or positron emission tomography \[PET\]/CT scan or magnetic resonance imaging \[MRI\] scan)
- •Absolute neutrophil count (ANC) \> 1000/uL
排除标准
- •Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for \>= 2 years or which will not limit survival to \< 2 years
- •A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib, or put the study outcomes at undue risk
- •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass
- •Central nervous system (CNS) involvement by lymphoma
- •Has a diagnosis of immunosuppression or is receiving ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of lymphoid cancer or other conditions
- •Note: subjects may use topical or inhaled corticosteroids or low-dose steroids (=\< 20 mg of prednisone or equivalent per day) as therapy for comorbid conditions; during study participation, subjects may also receive systemic or enteric corticosteroids as needed for treatment-related toxicities
- •Has an active autoimmune disease or history of autoimmune disease such as hepatitis, hypophysitis, nephritis, hyperthyroidism or hypothyroidism, interstitial lung disease, colitis
- •Requires or is currently receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug
- •Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
研究组 & 干预措施
Treatment (ibrutinib, nivolumab)
Patients receive ibrutinib PO QD on days 1-21 and nivolumab IV continuously over 60 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 16 courses and treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity.
干预措施: Ibrutinib
Treatment (ibrutinib, nivolumab)
Patients receive ibrutinib PO QD on days 1-21 and nivolumab IV continuously over 60 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 16 courses and treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
Treatment (ibrutinib, nivolumab)
Patients receive ibrutinib PO QD on days 1-21 and nivolumab IV continuously over 60 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 16 courses and treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab
结局指标
主要结局
Proportion of patients in CR
时间窗: Up to course 7 (147 days)
Simon's two-stage design will be used to test the null hypothesis that the true CR rate is =\< 20% versus the alternative hypothesis that the true CR rate is \>= 50%.
次要结局
- Incidence of adverse events measured by Common Terminology Criteria for Adverse Events version 4.03(Up to 3 years)
- Duration of response(From the first documentation of response (CR, partial response) to the first documentation of definitive disease progression or death from any cause, whichever occurs first, assessed up to 3 years)
- ORR(Up to 3 years)
- PFS(From the date of enrollment until the first documentation of objective disease progression or death from any cause, whichever occurs first, assessed up to 3 years)